Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols.
Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols.
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DOI：
10.2147/ijn.s30724
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发表时间：
2013
影响因子：
8
通讯作者：
Mansour HM
中科院分区：
文献类型：
--
作者：
Meenach SA;Vogt FG;Anderson KW;Hilt JZ;McGarry RC;Mansour HM
采用不同的磷脂配方和合理选择的喷雾干燥泵速，通过有机溶液、先进的闭式喷雾干燥工艺，合理配制了新型先进的雾化干燥和共喷雾干燥的模拟磷脂和聚乙二醇(PEG)基脂聚合物作为生物可降解生物相容脂聚合物的微粒/纳米干粉。将不同聚乙二醇长度的二棕榈酰磷脂酰胆碱(DPPC)和二棕榈酰磷脂酰乙醇胺聚乙醇胺(DPPE-PEG)的比例混合在稀甲醇溶液中。扫描电子显微镜图像显示可吸入颗粒物的光滑球形颗粒形态。用扫描电子显微镜和SigmaScan®软件对颗粒大小进行统计分析，确定其直径为600 nm~1.2μm，是深部肺泡穿透的最佳选择。用差示扫描量热法(DSC)和粉末X射线衍射法(PXRD)分别分析了固体相转变和分子长程有序性，证实了固体相中磷脂双层的存在。颗粒的残余水分含量很低，通过卡尔·费舍尔滴定进行了分析。用衰减全反射傅里叶变换红外光谱(ATR-FTIR)和共聚焦拉曼显微镜(CRM)确定了粒子的组成，化学成像证实了粒子的化学均一性。使用下一代撞击器™(NGI™)和HandiHaler®干粉吸入器设备来评估干粉气溶胶的分散性能，其中空气动力学质量中值直径在2.6到4.3μm之间，具有出色的气溶胶分散性能，例如发射剂量、细颗粒物分数和可吸入分数的高值。总体而言，确定了喷雾干燥过程中定义的泵速对固体颗粒特性有显著影响，并且较高的泵速产生最优的系统。成功地实现了用于靶向吸入干粉的先进的可吸入脂聚合物干粉吸入器。
Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved.